Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Irs1 serine 307 promotes insulin sensitivity in mice.

Cell metabolism | Jan 15, 2010

http://www.ncbi.nlm.nih.gov/pubmed/20074531

Phosphorylation of the insulin receptor substrates (Irs) on serine residues-typified by Ser307 of rodent Irs1-is thought to mediate insulin resistance. To determine whether Ser307 negatively regulates Irs1 in vivo, we generated knockin mice in which Ser307 (human Ser312) was replaced with alanine (A/A). Unexpectedly, A/A mice that were fed a high-fat diet developed more severe insulin resistance than control mice, accompanied by enhanced pancreatic compensation and impaired muscle insulin signaling. Chow-fed mice whose livers lacked Irs2 but retained a single knockin allele (A/lox::LKO2) were profoundly insulin resistant (versus +/lox::LKO2 mice), and their hepatocytes showed impaired insulin signaling ex vivo. Similarly, mutant A307 Irs1 adenovirus only partially restored the response to injected insulin in mice lacking hepatic Irs1 and Irs2. Thus, contrary to the results of cell-based experiments, Ser307 in mice is a positive regulatory site that moderates the severity of insulin resistance by maintaining proximal insulin signaling.

Pubmed ID: 20074531 RIS Download

Mesh terms: Amino Acid Substitution | Animals | Dietary Fats | Gene Knock-In Techniques | Insulin | Insulin Receptor Substrate Proteins | Insulin Resistance | Mice | Serine | Signal Transduction

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NIDDK NIH HHS, Id: DK43808
  • Agency: NIDDK NIH HHS, Id: R01 DK038712
  • Agency: NIDDK NIH HHS, Id: R01 DK038712-20
  • Agency: NIDDK NIH HHS, Id: R01 DK038712-21
  • Agency: Howard Hughes Medical Institute, Id:

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.